Kidney failure can cause accumulation in body fluids, such as blood, of toxins and derivatives and metabolites of organic drugs taken by the patient. Sorbent dialysis systems provide treatment for patients with acute or chronic kidney disease. Dialysate is delivered to a dialyzer in prescribed amounts to cleanse the blood of impurities, correct the patient's body chemistry, and remove excess fluid. In sorbent dialysis, a sorbent cartridge can purify the initial dialysate and continuously regenerate spent dialysate throughout the treatment. This can significantly reduce the volume of dialysate needed for dialysis. Closed loop multi-pass sorbent based dialysis systems, for example, regenerate dialysate for reuse by passing spent dialysate through a regeneration section comprising at least one sorbent cartridge and suitable additives. Spent dialysate comprising urea, which is diffused from impure blood in the dialyzer, passes through conventional sorbent cartridges. The sorbent cartridges bind uremic wastes, and also can be used for other tasks, such as balancing dialysate pH. A typical sorbent cartridge system can include, for example, an activated charcoal layer (a purification layer), a urease enzyme layer (a conversion layer), a cation exchange layer, and an anion exchange layer. The REDY™ (REgenerative DialYsis) System is an example of a commercially available sorbent cartridge system which incorporates such an arrangement of filtration and sorbent materials. During regenerative dialysis, the used or spent dialysate can move up through the layers of the cartridge and a high purity regenerated dialysate can emerge from the cartridge outlet for recirculation to the dialyzer. The activated charcoal or carbon layer can be used to absorb organic metabolites such as creatinine, uric acid, and nitrogenous metabolic waste of the patient as well as chlorine and chloramines from the water. Urease used in the urease layer can be an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. Ammonium carbonate is released by a urease layer in a conventional sorbent cartridge. Ammonium created in the urease layer can be removed in the cation exchange layer, e.g., an adsorbent zirconium phosphate, in exchange for release of Na+ and H+ ions. The carbonate from the urea hydrolysis then can combine with H+ to form bicarbonate (HCO3−) and carbonic acid (H2CO3). Carbonic acid is an unstable organic acid; most of it rapidly breaks down into water and carbon dioxide molecules (CO2). The anion exchange layer, e.g., HZO containing acetate as a counter ion, can remove HCO3−, P−, and other anions (e.g., F− in water), and releases acetate. The CO2 gas bubbles are vented from the cartridge.
The present investigators have recognized that conventional sorbent dialysis using an immobilized urease layer in the sorbent cartridge can have disadvantages, such as needing a significant volume of water in the dialysate, ammonia leakage and monitoring requirements, variations of Na and bicarbonate in dialysate, high PCO2 in dialysate, acetate and soluble Al and Zr leakages, concanavalin from Jack Bean meal, bacterial and endotoxin removal needs, high pressure problems, insufficient regenerated dialysate quality, and the need for the immobilized urease layer itself. The present investigators have specifically recognized that conventional sorbent dialysis using an immobilized urease layer may require upwards to about 6 liters water in the dialysate to minimize variation of sodium (Na+) and bicarbonate ions (HCO3−) caused by interaction of the enzymatic hydrolysis products of urea (e.g., ammonia carbonate as ammonium (NH4+) and carbonate (CO3−2)) in dialysate with zirconium sorbent (e.g., ZrP), which adsorbs ammonia in exchange for release of sodium and hydrogen ions from the sorbent material. The present investigators further have recognized that it would desirable to eliminate the foregoing disadvantages while simultaneously providing sorbent dialysis which is effective to regenerate spent dialysate or purify dialysate or water to make up dialysate by removing uremic toxins therefrom with non-enzymatic urea binders.